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Biomedical subjects

G Collier

Publications and source records attributed to G Collier.

At least 19 recordsLinked to original sources
PubMed2003

The Taq IA and Ser311 Cys polymorphisms in the dopamine D2 receptor gene and obesity.

Dopamine D2 receptors (DRD2) in the central nervous system are involved in the regulation of feeding. It remains to be elucidated if mutations in the DRD2 gene contribute to the development of obesity. The aim of the present study was to investigate whether the Taq IA and Ser311Cys polymorphisms in the DRD2 gene are associated with obesity in Nauruan and Australian subjects. Subjects were selected based on extremes of the body mass index (BMI) distribution. Two groups of Australian women were selected. The leanest group had a mean BMI of 22.5 kg/m2 (range: 20.3-24.3) and the heaviest group had a mean of 36.1 kg/m2 (32.5-44.1). Four groups of Nauruan subjects were selected. Leanest men had a mean BMI of 33.0 kg/m2 (28.4-36.9), heaviest men had a mean of 52.8 kg/m2 (46.5-69.2), leanest women had a mean of 34.8 kg/m2 (28.2-41.8) and heaviest women had a mean of 55.1 kg/m2 (49.3-73.8). Subjects were genotyped for the Taq IA and Ser311Cys polymorphisms using polymerase chain reaction (PCR) restriction fragment length polymorphism analysis and allelic discrimination Taqman PCR respectively. Leanest and heaviest groups were examined for differences in genotype frequency. Taq IA and Ser311Cys genotype frequencies did not differ significantly between leanest and heaviest Nauruan groups, or between leanest and heaviest Australians. Haplotype frequencies of these polymorphisms did not differ between leanest and heaviest groups. The Taq IA and Ser311Cys polymorphisms in the DRD2 gene are unlikely to be common causes of obesity in these populations.

Adult↗
PubMed2002

Calpain 3 gene expression in skeletal muscle is associated with body fat content and measures of insulin resistance.

OBJECTIVE: To investigate whether skeletal muscle gene expression of calpain 3 is related to obesity and insulin resistance. DESIGN: Cross-sectional studies in 27 non-diabetic human subjects and in Psammomys obesus, a polygenic animal model of obesity and type 2 diabetes. MEASUREMENTS: Expression of CAPN3 in skeletal muscle was measured using Taqman fluorogenic PCR. In the human subjects, body composition was assessed by DEXA and insulin sensitivity was measured by euglycemic-hyperinsulinemic clamp. In Psammomys obesus, body composition was determined by carcass analysis, and substrate oxidation rates, physical activity and energy expenditure were measured by whole-body indirect calorimetry. RESULTS: In human subjects, calpain 3 gene expression was negatively correlated with total (P = 0.022) and central abdominal fat mass (P = 0.034), and with blood glucose concentration in non-obese subjects (P = 0.017). In Psammomys obesus, calpain 3 gene expression was negatively correlated with circulating glucose (P = 0.013) and insulin (P = 0.034), and with body fat mass (P = 0.049). Indirect calorimetry revealed associations between calpain 3 gene expression and carbohydrate oxidation (P = 0.009) and energy expenditure (P = 0.013). CONCLUSION/INTERPRETATION: Lower levels of expression of calpain 3 in skeletal muscle were associated with reduced carbohydrate oxidation and elevated circulating glucose and insulin concentrations, and also with increased body fat and in particular abdominal fat. Therefore, reduced expression of calpain 3 in both humans and Psammomys obesus was associated with phenotypes related to obesity and insulin resistance.

Adipose Tissue↗
PubMed2001

Taste, intake rate, and food choice in rats.

The contribution of taste to the food choices of foraging rats was examined. Rats in a laboratory foraging paradigm searched for sequential opportunities to eat at two feeders containing chow-based food pellets that were plain or flavored with saccharin or citric acid. Pellets cost the same number of bar presses at both feeders. Saccharin adulteration had no effect on intake parameters. Citric-acid-flavored pellets were eaten more slowly and in smaller meals. If there was no alternative food, daily intake was slightly reduced. When the alternative food was plain, fewer meals and fewer pellets were taken of the citric-acid-flavored than plain pellets. When we gradually increased the price of the plain pellets at one feeder, while the price at the alternative feeder (which contained either plain or citric-acid-flavored pellets) remained low, the rate of eating (profitability) decreased at the higher-price feeder, and the rats shifted their intake toward the less-costly, more profitable pellets. We compared the relationship between the relative eating rate at each feeder and the relative meal size (or daily intake) at each feeder when the low-priced food was plain and when it was flavored with citric acid, and found no differences. This indicates that taste may influence choice via its effect on rate of intake.

Animals↗
PubMed2000

Sucrose intake as a function of its cost and the cost of chow.

The avid consumption of pure carbohydrate solutions, which often results in a distortion of nutrient balance, is generally presumed to be driven by their taste. In the first of two experiments, we examined the effect of consumption cost on rats' intake of three concentrations of sucrose solution (8%, 16%, and 32%) when a nutritionally complete chow was concurrently freely available. In the second experiment, we examined the intake of 24% sucrose solution and chow as the consumption costs of both were varied. Increasing the cost of sucrose resulted in a reduction in the percent calories taken from sucrose; the steepness of the decline in intake with price was inversely related to the sucrose concentration and to the cost of chow. Chow calories were substituted for relatively expensive sucrose calories. An increase in the cost of chow resulted in a reduction in the percent of calories taken from chow and a protein-poor diet. The cost of sucrose did not affect the slope of the chow intake curve, presumably because, despite its sweet taste, sucrose was not a substitute for the protein, fat, and micronutrients in chow. Total caloric intake was conserved in all cases.Thus, the avid consumption of sucrose solution is curtailed when it is costly; but the degree of change in intake with cost depends on the cost of an alternative food. These results suggest that diet selection involves a comparison not only of the taste and post-ingestive consequences of available foods, but also of the cost of calories and nutrients in the foods. Selection appears to be guided first by caloric requirements and the relative cost of calories, then by nutrient requirements and the relative cost of nutrients, and finally by taste.

Animals↗
PubMed2000

Effects of exercise on GLUT-4 and glycogenin gene expression in human skeletal muscle.

To investigate the effect of exercise on GLUT-4, hexokinase, and glycogenin gene expression in human skeletal muscle, 10 untrained subjects (6 women and 4 men, 21.4 +/- 1.2 yr, 66.3 +/- 5.0 kg, peak oxygen consumption = 2.30 +/- 0.19 l/min) exercised for 60 min on a cycle ergometer at a power output requiring 73 +/- 4% peak oxygen consumption. Muscle samples were obtained by needle biopsy before, immediately after, and 3 h after exercise. Gene expression was quantified, relative to 29S ribosomal protein cDNA, by RT-PCR. GLUT-4 gene expression was increased immediately after exercise (1.7 +/- 0.4 vs. 0.9 +/- 0.3 arbitrary units; P < 0.05) and remained significantly higher than baseline 3 h after the end of exercise (2. 2 +/- 0.4 vs. 0.9 +/- 0.3 arbitrary units; P < 0.05). Hexokinase II gene expression was significantly higher than the resting value 3 h after the end of exercise (2.9 +/- 0.4 vs. 1.3 +/- 0.3 arbitrary units; P < 0.05). Exercise increased glycogenin mRNA more than twofold (2.8 +/- 0.6 vs. 1.2 +/- 0.2 arbitrary units; P < 0.05) 3 h after the end of exercise. For the first time, we report that a single bout of exercise is sufficient to cause upregulation of GLUT-4 and glycogenin gene expression in human skeletal muscle. Whether these increases, together with the associated increase in hexokinase II gene expression, lead to increased expression of these key proteins in skeletal muscle and contribute to the enhanced skeletal muscle glucose uptake, glycogen synthesis, and insulin action observed following exercise remains to be determined.

Adult↗
PubMed1999

Behavioral strategies in the cold: effects of feeding and nesting costs.

Animals can meet energetic challenges by acquiring or conserving energy. In the present experiment, we pitted these strategies against each other by housing rats in a cold environment and requiring them to bar press for food pellets and for access to a heated nest. Our question was how rats would exploit these resources to meet the added energetic demand of the cold when food was abundant or scarce. Results showed that rats' allocation of time and effort between competing activities was a function of demand. Feeding and nesting were partially substitutable in the cold: rats traded food for warmth and vice versa, economizing on both time and energy by adjusting their feeding and nesting patterns. Depending upon food abundance and the cost of nesting, rats acquired calories from food, conserved calories by nesting, and borrowed calories from the defense of body weight.

Acclimatization↗
PubMed1999

Prey size and prey density affect meal patterns of rats in depleting and nondepleting patches.

We examined meal-ending decisions by rats feeding in depleting patches (where the rate of return decreased during a meal) and nondepleting patches (where the rate of return was constant) in a closed-economy, laboratory setting that allowed the precise measurement of feeding rates and meal patterns. The rats were free living in an environment where costs were imposed with bar-press requirements for (1) travelling to a patch to begin a meal and (2) earning prey during the ensuing meal in that patch. The prey in each patch were large or small, and dense or sparse. In both depleting and nondepleting patches, meals were larger as travel price increased. In nondepleting patches, meal size (in grams) was unaffected by the rate of return within the patch, but in depleting patches, meals were larger where the rate of return was higher. In depleting patches, the rats ate the same number of small and large prey per meal, suggesting that meals end when the rate of return reaches some level relative to a comparison value; however, the end-of-meal rate was lower than the average rate (calculated over foraging and feeding time), and thus meals were too large to maximize rate or minimize cost. No obvious rule of thumb explained meal size in both depleting and nondepleting patches. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1999

The relation between meal size and the time between meals: effects of cage complexity and food cost.

Certain popular models of the regulation of food intake predict a positive correlation between the size of a meal and the preceding and/or following intermeal interval. However, the reported strength of these prandial correlations has varied widely in the literature. To determine what factors may influence the strength of these relationships, we measured the timing of and amount consumed in meals of laboratory rats as a function of 1) whether they were housed in isolation or with partial access to peers or a running wheel, 2) whether they were disturbed daily or weekly for maintenance procedures, and 3) whether food was free or contingent on operant responding. We also compared two definitions of "meal" and "intermeal interval." Strong prandial correlations were found only occasionally. Caging, food cost, and maintenance frequency did not affect the size of the correlations, although these factors did influence the rats' meal patterns. We conclude the regulation of food intake cannot be explained by models relying on a regular relationship between meal size and intermeal interval.

Analysis of Variance↗
PubMed1999

Cigarette smoking, alcohol use, and physical activity in relation to serum leptin levels in a multiethnic population: The Miami Community Health Study.

PURPOSE: To examine the correlates of plasma leptin, including fasting insulin, adiposity, and several health habits and behaviors among a nondiabetic multiethnic population. METHODS: A cross-sectional study was conducted among 25-44 year old African-Americans (n = 126), Cuban-Americans (n = 107), and non-Hispanic whites (n = 189) randomly selected from Dade County Florida. Fasting leptin levels were correlated with fasting insulin, percent body fat, smoking, alcohol use, and physical activity within each sex. Multiple linear regression and analysis of covariance were used to estimate the independent determinants of plasma leptin concentration separately among men and women. RESULTS: Stepwise linear regression analyses revealed statistically significant associations of leptin with percent body fat, fasting insulin, cigarette smoking, and physical activity (both inversely) among men (p < 0.05 for each). Among women, percent body fat, fasting insulin (both positively), cigarette smoking, and alcohol use (inversely) were independent predictors of leptin levels explaining over 70% of the variance. Analyses of covariance revealed that women had higher adjusted mean leptin levels than men (13.1 ng/ml vs. 5.9 ng/ml; p < 0.001), whereas no separate effect of ethnicity was noted. CONCLUSIONS: Although adiposity was the strongest correlate of leptin levels, fasting insulin and several health habits and behaviors were independently associated with leptin. After adjustment for these factors, women had significantly higher mean leptin levels than men. The independent association among leptin and insulin levels is intriguing and suggests additional avenues for epidemiologic research.

Adult↗
PubMed1999

Neural mechanisms in human obesity-related hypertension.

OBJECTIVE: Two hypotheses concerning mechanisms of weight gain and of blood pressure elevation in obesity were tested. The first hypothesis is that in human obesity sympathetic nervous system underactivity is present, as a metabolic basis for the obesity. The second hypothesis, attributable to Landsberg, is that sympathetic nervous activation occurs with chronic overeating, elevating blood pressure. These are not mutually exclusive hypotheses, since obesity is a heterogeneous disorder. DESIGN AND METHODS: Whole body and regional sympathetic nervous system activity, in the kidneys and heart, was measured at rest using noradrenaline isotope dilution methodology in a total of 86 research voluteers in four different subject groups, in lean and in obese people who either did, or did not, have high blood pressure. RESULTS: In the lean hypertensive patients, noradrenaline spillover for the whole body, and from the heart and kidneys was substantially higher than in the healthy lean volunteers. In normotensive obesity, the whole body noradrenaline spillover rate was normal, mean renal noradrenaline spillover was elevated (twice normal), and cardiac noradrenaline spillover reduced by approximately 50%. In obesity-related hypertension, there was elevation of renal noradrenaline spillover, comparable to that present in normotensive obese individuals but not accompanied by suppression of cardiac noradrenaline spillover, which was more than double that of normotensive obese individuals (P<0.05), and 25% higher than in healthy volunteers. There was a parallel elevation of heart rate in hypertensive obese individuals. CONCLUSIONS: The sympathetic underactivity hypothesis of obesity causation now looks untenable, as based on measures of noradrenaline spillover, sympathetic nervous system activity was normal for the whole body and increased for the kidneys; the low sympathetic activity in the heart would have only a trifling impact on total energy balance. The increase in renal sympathetic activity in obesity may possibly be a necessary cause for the development of hypertension in obese individuals, although clearly not a sufficient cause, being present in both normotensive and hypertensive obese individuals. The discriminating feature of obesity-related hypertension was an absence of the suppression of the cardiac sympathetic outflow seen in normotensive obese individuals. Sympathetic nervous changes in obesity-related hypertension conformed rather closely to those expected from the Landsberg hypothesis.

Adolescent↗
PubMed1999

Leptin is released from the human brain: influence of adiposity and gender.

Leptin, a 16-kDa circulating protein primarily derived from adipocytes, is an important factor in the regulation of appetite and energy expenditure. Using simultaneous arterio-venous blood sampling, several organs were assessed with regard to their individual roles in leptin metabolism in healthy male and female subjects constituting a range of body mass indices. Plasma leptin levels were unchanged after passage through the hepatosplanchnic and forearm circulations. In contrast, concentrations in the renal vein were consistently lower than those in the renal artery (-15%; P<0.005), indicating net extraction, whereas the brain was observed to be a net leptin releaser. Concentrations in the internal jugular vein were significantly higher than arterial levels in lean females (change, 3.0+/-1.2 ng/mL; P<0.02) and in obese males (body mass index, >28 kg/m2), but not lean (change, 2.3+/-2.3 vs. 0.1+/-0.1 ng/mL, respectively; P<0.05), indicating a probable influence of both gender and adiposity on brain leptin release. An attempt to grossly localize the site of brain release by using cerebral venous scans to distinguish between jugular venous drainage from cortical and subcortical brain areas revealed no region-specific secretion. These data raise the possibility that the brain is a nonadipose source of leptin. In addition, the higher level of brain release observed in females may contribute to the well documented gender differences in overall plasma leptin levels.

Adipose Tissue↗
PubMed1999

Clinical efficacy of metformin against insulin resistance parameters: sinking the iceberg.

It has been increasingly recognised in recent years that type 2 (non-insulin-dependent) diabetes is part of a cluster of cardiovascular risk factors known as the metabolic syndrome, but also endorsed with such names as the deadly quartet, syndrome X and the insulin resistance syndrome. Atherosclerosis is the most common complication of type 2 diabetes among Europeans, and coronary artery, cerebrovascular and peripheral vascular disease are 2 to 5 times more common in people with this condition than in those without diabetes. These observations indicate that the treatment of type 2 diabetes requires agents that do more than simply lower blood glucose levels, and a therapy with both antihyperglycaemic effects and beneficial effects on dyslipidaemia, hypertension, obesity, hyperinsulinaemia and insulin resistance is likely to be most useful. In this respect, metformin has an important and established role: this drug has been shown to lower blood glucose and triglyceride levels, and to assist with weight reduction and to reduce hyperinsulinaemia and insulin resistance. Studies in the Israeli sand rat, Psammomys obesus, have indicated hyperinsulinaemia/insulin resistance to be the initial and underlying metabolic disorder in obesity and type 2 diabetes. Thus, the well established effect of metformin in reducing insulin resistance makes this drug an excellent candidate for the prevention of progression of impaired glucose tolerance to type 2 diabetes, and for the reduction of mortality associated with cardiovascular disease.

Animals↗
PubMed1999

Is fasting leptin associated with insulin resistance among nondiabetic individuals? The Miami Community Health Study.

OBJECTIVE: Whether serum leptin levels are associated with insulin resistance independent of the effects of hyperinsulinemia and adiposity is an important unanswered question. We examined the relationship between the rate of insulin-mediated glucose uptake and serum leptin concentrations among nondiabetic men and women. RESEARCH DESIGN AND METHODS: A cross-sectional analysis was performed among 49 young to middle-aged men and women who participated in the Miami Community Health Study. All participants had measures of insulin resistance (euglycemic-hyperinsulinemic clamp), postchallenge insulin levels, fasting serum leptin levels, and several measures of adiposity. RESULTS: The rate of insulin-mediated glucose uptake (M in milligrams per kilogram per minute) was significantly associated with leptin concentrations in both men (r = -0.83; P < 0.001) and women (r = -0.59; P < 0.001). M was also inversely related to percent body fat and to the 2-h insulin area under the curve (AUC). After covariate adjustment for sex, percent body fat, and AUC, leptin remained a significant correlate of M (P = 0.04). CONCLUSIONS: Cross-sectionally, leptin was significantly associated with insulin resistance in this nondiabetic sample of men and women. There may be a different physiological mechanism to explain the leptin/insulin resistance association apart from the insulin/adiposity link. Confirmatory evidence awaits the results of clinical trials.

Adult↗
PubMed1998

Arterial compliance, blood pressure, plasma leptin, and plasma lipids in women are improved with weight reduction equally with a meat-based diet and a plant-based diet.

Obesity, strongly associated with the risk for coronary heart disease (CHD), is becoming increasingly prevalent. This study was designed to establish first whether systemic arterial compliance (SAC), an index of arterial function, is improved with weight loss and second, whether cardiovascular risk factors that improve with weight loss are reduced equally with lean meat or with an equivalent amount of plant protein in the diet. Thirty-six women, mostly overweight or obese, aged 40+/-9 years, were allocated nonrandomly to a 16-week parallel-design trial of two equienergetic diets designed to lead to weight loss, with one arm of the study emphasizing red meat and the other soybeans as the major protein source. Body weight, waist and hip circumference, and plasma lipids, glucose, insulin, and leptin levels were measured, and SAC was calculated from ultrasound measurement of aortic flow velocity and aortic root driving pressure. Subjects lost weight (9% of body weight in 16 weeks) and showed decreased plasma total and low-density lipoprotein (LDL) cholesterol (12% and 14%, P < .0001, respectively), triacylglycerol (17%, P < .05), and leptin (24%, P < .01) concentrations. However, lipoprotein(a) [Lp(a)] levels did not change significantly. Mean arterial pressure (MAP) decreased 7% and SAC increased 28% (P < .001 for both). However, only the decrease in arterial pressure correlated significantly with the reduction in the waist to hip ratio (WHR), and the improvement in SAC correlated inversely with the blood pressure reduction (P < .001 for both). Further, weight loss and the metabolic benefits of weight loss occurred equally with the meat-based and plant-based diets. We conclude that moderate weight loss in women leads to a substantial reduction in the cardiovascular risk, including SAC.

Adult↗
PubMed1998

Examination of the self-selected fluid intake practices by junior athletes during a simulated duathlon event.

Thirty-two elite junior athletes in two age categories, older than or equal to 15 years old (O15) (8 females and 9 males) and less than 15 years old (U15) (8 females and 7 males), performed a laboratory-based duathlon (run-ride-run). At the completion of the event, significant body mass losses were recorded for all groups. Compared with the other three groups, the O15 males lost body mass at a greater absolute rate (1.26 +/- 0.06 kg.hr-1 vs. a mean of 0.62 +/- 0.11 kg.hr-1 for the other three groups) and a greater relative rate (1.95 +/- 0.10%BM.hr-1 vs. a mean of 1.23 +/- 0.19%BM.hr-1 for the other three groups) (p < .05). No differences were observed between groups for fluid consumption. Subjects consumed more fluid (p < .05) during the cycle phase and postevent than preevent or during the run phases. Results indicated that the athletes' fluid intake practices were insufficient to maintain adequate hydration during the simulated event.

Adolescent↗
PubMed1998

Patch choice as a function of procurement cost and encounter rate.

The effects of patch encounter rate on patch choice and meal patterns were studied in rats foraging in a laboratory environment offering two patch types that were encountered sequentially and randomly. The cost of procuring access to one patch was greater than the other. Patches were either encountered equally often or the high-cost patch was encountered more frequently. As expected, rats exploited the low-cost patch on almost 100% of encounters and exploited the high-cost patch on a percentage of encounters that was inversely proportional to its cost. Meal size was the same at both patches. Surprisingly, when low-cost patches were rare, the rats did not increase their use of high-cost patches. This resulted in spending more time and energy searching for patches and a higher average cost per meal. The rats responded to this increased cost by reducing the frequency and increasing the size of meals at both patches and thereby limited total daily foraging cost and conserved total intake.

Animals↗
PubMed1997

Who is in charge? Animal vs experimenter control.

In the 1920s Curt Richter (1927) stated that the central problem for psychology was to discover the determinants of the initiation and termination of bouts of behavior. Ignoring this challenge, experimentation in animal psychology has been dominated by the session paradigm in which animals work in brief sessions for a resource of which they have been deprived. In this open economy, no behavioral strategy of the animal can meet its demand, and the beginnings and ends of bouts are controlled by the experimenter; thus, Richter's problem cannot be addressed. In contrast, in a free-feeding, closed economy, the animal controls the initiation and termination of feeding and can regulate its intake, and bout patterns can be observed. If the paradigm is modified to simulate a habitat where resources are distributed discontinuously and the animal must work to discover and procure access to a commodity before it can be used, behavioral strategies allowing the animal to regulate its intake while tending to maximize the ratio of benefits to costs are revealed. We offer an answer to Richter's question based on a cost/benefit analysis of feeding behavior in this foraging paradigm. We show that the time and energy costs of resource acquisition and resource consumption are powerful determinants of the pattern of resource use, and that they have different and independent effects. The former costs are reduced by reducing the frequency of initiating bouts, and the latter costs, by altering the rate and amount of consumption. Further, the time window of these relations is much longer than expected from analyses in the session paradigm. We conclude that the recurrent nature of behavior is due to the discontinuous distribution of resources rather than to cycles of physiological depletion and repletion, and that the determinants of bout initiation and termination lie in the economics of the allocation of time and effort to different resources and activities.

Animals↗